Replies to post #46970 on Biotech Values

[bobrmd]

If you think that pfs for gemzar is significant then you cant see the forrest through the trees. The fda may approve satraplatin for a 10 day increasse in median survival. Gemzar failed in the adjuvant trials. PFS just means that some patients prohressed earlier in the control arm. They didnt live longer and with the side effects of gemzar yous have a hard time convincing me that it is of any great benefit. and it is expensive.

I treat these patients and I wish we had something better. These drugs are approved primarily as a compassionate gesture on the part of the fda (i use the word compassion loosely here) after some meaningless endpoint is met.

Two wrongs dont make a right and provenge does have stat problems but it is hard to ignore overall survival. The fda should cut dendreon some slack because if it really does improve survival by 23% that would be remarkable abd a shame that patients are now deprived of that chance.

[p3analyze]

"hence, lengthening the time to progression confers a very meaningful QoL benefit."

laughable statement. QOL measures the symptomatic, physical, psychological wellbeing and social functioning, wherease TTP measures the radiological component. Gemzar did not improve QOL so its label does not allow such a claim. The oncologists on ODAC voted 9-2 against approval, period, if that does not represent opinion of oncology community, I don't what does! Maybe they should invite CTGTAC to vote on ODAC?

Gemzar is a great drug- but in the case of ovarian, FDA bent its rule, the blame was conviently shifted to Von Eschenbach.

PGS and DEW should read the article below to hear the other side of the argument regarding the fallacy of delaying time to further chemotherapy.
http://findarticles.com/p/articles/mi_m0ISW/is_280/ai_n16850472

[gofishmarko]

>> You appear to have been brainwashed by DNDN bulls into believing that survival is the only efficacy metric of consequence in cancer. <<

The thing I like about that statement is that , of necessity , it implies that I have a brain , that could then be "washed". Therefore I'm interpreting it as a well-camouflaged , but nonetheless sincere , compliment. Thank you.

The following passages from the pre-ODAC FDA briefing document have relevance to the Gemzar discussion ( comments in italics are mine ):

EXECUTIVE SUMMARY

Gemzar was studied in a randomized Phase 3 study of 356 patients with advanced ovarian cancer that had relapsed at least 6 months after first-line platinum-based therapy. Patients were randomized 1:1 to receive either Gemzar in combination with carboplatin or carboplatin alone. The
Gemzar/carboplatin combination adds 2.8 months to median progression-free survival (PFS) with no apparent effect on survival at a cost of increased toxicity, mainly anemia, neutropenia and thrombocytopenia, requiring increased RBC and platelet transfusions and increased use of granulocyte stimulating factors and erythropoietic agents. Independently assessed tumor response rates were Gemzar/carboplatin 46.3% and carboplatin alone 35.6%. This trial was conducted entirely outside of the United States and the FDA had no input into its design or conduct.

The main issue is whether adding 2.8 months to median PFS at a cost of additional toxicity with no apparent effect on survival is a sufficient basis for Gemzar approval for this use. Important considerations are that the combination of paclitaxel and carboplatin has been shown to prolong
survival in this setting.( Increased survival ? We mustn't have that !) In addition, a large international gynecologic group (including the NCI, GOG, RTOG and NCIC) at a Consensus Conference on Ovarian Cancer in 2004 indicated that in the setting of second-line chemotherapy for advanced ovarian cancer "progression-free survival does not seem to be a good surrogate for survival". "Progression-free survival data remain of interest but are unlikely to be sufficiently
persuasive to shift practice patterns".
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"It does not appear that differences in post study chemotherapy account for the failure to demonstrate a Gemzar survival effect."
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Quality of Life

Health-related quality of life (HRQL) was assessed using the EORTC QLQ-C30 and the EORTC QLQ-OV28 patient reported outcome (PRO) questionnaires. These HRQL assessments can not be used as the basis of Gemzar approval because the study was not blinded( ! ), the effect of concurrent medications was not assessed( !! ), on some items the carboplatin alone group did better( !!! ) and the effect on "global quality of life," although statistically significant, is not clinically meaningful.
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RECOMMENDATION
Deferred pending advice of the ODAC.
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As we know , ODAC voted 9 to 2 against approval , but the von E-led FDA , upon reviewing additional information provided by Lilly , could see no reason to deny approval of this wonder-drug. What was the additional info ? Unknown , since it was not made part of the public record. Rumors suggest it was voluminous , however , and was of the " unmarked , small-denomination " variety , whatever that means. The U.S. is in the decided minority , I'm sure , if we're not the only country to have approved Gemzar for this indication.

So , the question for me is : Do I trust more in groupthink , as exemplified by the FDA reviewer quoted above , the ODAC panel , and some current Dendreonites , or do I trust in Dew-think , as exemplified by the scientific genius of Dr. von E ? ( I'm making an assumption as to von E's genius , but a safe one I believe , given the widely-accepted truism that all Bush appointees share this trait , along with the complimentary one of utmost personal integrity. )

What to do ? Hmmm , let me think about it a se... Ok, I've decided. I'm sticking with groupthink. Sorry , Dew.

BTW , Dew , in light of the liberties I took in interpretation of your comment above , and in the interest of fairness and reciprocity , please feel free to interpret my comments in any way that suits you , as well.

Regards , gofish.